Protein Gadd45a Is to Blame for Muscle Atrophy

Researchers in Iowa have made major progress in determining what causes muscle atrophy. Athletes often experience this when recovering from an injury. During recovery the muscles they are not able to use atrophy, thus extending the recovery process in order to build muscles back up. Until now, little has been known about what causes the skeletal muscles to atrophy.

The team of researchers in Iowa has identified a single protein, called Gadd45a, as the culprit. It orchestrates 40% of the gene activity which ultimately causes skeletal muscle to atrophy. The researchers also discovered that Gadd45a works inside the muscle cell’s nucleus and reprograms hundreds of genes to change the shape of the nucleus.1

“We now understand a key molecular mechanism of skeletal muscle atrophy,” says Christopher Adams, associate professor of internal medicine at the University of Iowa and corresponding author on the paper published in the Journal of Biological Chemistry. “This finding could help us find a therapy for treating muscle atrophy in patients, and we now know a great place to start is by reducing Gadd45a.”2

Previous research found that when skeletal muscle is stressed due to malnutrition, nerve damage, or inactivity, production of a protein called ATF4 is increased. This protein initiates muscle atrophy by activating genes, but the mechanisms were vague. The same scientists, Christopher Adams, led a team of researchers who conducted experiments to discover the ATF4 target genes. Their research revealed that ATF4 caused muscle atrophy by activating the Gadd45a gene.3

Additionally, they discovered Gadd45a affects muscles in two main ways that result in muscle atrophy:4

It instructs muscle cells to produce fewer proteins that are needed to maintain muscle.

It causes proteins already existing in muscle fibers to break down.

“To put this all together, it means Gadd45a is going into the muscle nucleus, and it totally changes it, so much so that the changes are visible. It’s turning genes on, and it’s turning genes off. It’s changed the cell. Gadd45a is like a central switch for muscle atrophy. If you can block it, you can conceivably stunt muscle atrophy to a large extent,” Adams said.5

Now that the door has been opened as to how muscle atrophy occurs, more research is needed to determine just how to stop the activation of Gadd45a. These findings are promising in the fact that researchers are on the verge of discovering just how to prevent or mitigate the effects of muscle atrophy. This not only could benefit the recovering athlete, but also the elderly and the ill.6